Visualizing the microtubule-associated protein tau in the nucleus

Lu, Jing, Li, Ting, He, RongQiao, Bartlett, Perry F. and Gotz, Jürgen (2014) Visualizing the microtubule-associated protein tau in the nucleus. Science China Life Sciences, 57 4: 422-431. doi:10.1007/s11427-014-4635-0

Author Lu, Jing
Li, Ting
He, RongQiao
Bartlett, Perry F.
Gotz, Jürgen
Title Visualizing the microtubule-associated protein tau in the nucleus
Journal name Science China Life Sciences   Check publisher's open access policy
ISSN 1674-7305
Publication date 2014-04-01
Year available 2014
Sub-type Article (original research)
DOI 10.1007/s11427-014-4635-0
Open Access Status DOI
Volume 57
Issue 4
Start page 422
End page 431
Total pages 10
Place of publication Beijing, China
Publisher Zhongguo Kexue Zazhishe / Science in China Press
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
2300 Environmental Science
1100 Agricultural and Biological Sciences
Abstract Although tau is mainly known as an axonal microtubule-associated protein, many studies indicate that it is not restricted to this subcellular compartment. Assessing tau's subcellular distribution, however, is not trivial as is evident from transgenic mouse studies. When human tau is over-expressed, it can be immunohistochemically localized to axons and the somatodendritic domain, modeling what is found in neurodegenerative diseases such as Alzheimer's disease. Yet, in wild-type mice, despite its abundance, tau is difficult to visualize even in the axon. It is even more challenging to detect this protein in the nucleus, where tau has been proposed to protect DNA from damage. To establish a framework for future studies into tau's nuclear functions, we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain. While depending on the fixation and permeabilization protocol, we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells, we failed to do so in N2a murine neuroblastoma cells. As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form. When either full-length or truncated human tau was expressed, both accumulated in the cytoplasm, but were also found in the nuclear fraction. Because subcellular fractionation methods have their limitations, we finally isolated nuclei to probe for nuclear tau and found that the nuclei were free of cytoplasmic contamination. Together our analysis identifies several protocols for detecting tau in the nucleus where it is found in a less phosphorylated form.
Keyword Alzheimer's disease
Microtubule-associated protein
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
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